Dr Garje on Selecting Between PARP Inhibitor Combinations in mCRPC

Rohan Garje, MD, chief, Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute, discusses considerations when choosing between FDA-approved PARP inhibitor–based combinations for patients with metastatic castration-resistant prostate cancer (mCRPC).

Notable treatment modality advancements have emerged for patients with mCRPC, Garje says. The phase 3 MAGNITUDE trial (NCT03748641) investigated the combination of niraparib (Zejula) and abiraterone acetate (Zytiga). Similarly, the phase 3 TALAPRO-2 trial (NCT03395197) explored talazoparib (Talzenna) in combination with enzalutamide (Xtandi), and the phase 3 PROpel trial (NCT03732820) assessed olaparib (Lynparza) plus abiraterone acetate. These trials collectively evaluated the efficacy of PARP inhibitors in combination with androgen receptor pathway inhibitors in the first-line mCRPC setting, and their outcomes emphasize the importance of patient selection to optimize treatment outcomes, Garje explains.

All 3 studies successfully met their primary end point of radiographic progression-free survival, and demonstrated overall survival (OS) benefits with the PARP inhibitors. Patients harboring BRCA1/2 mutations derived the greatest OS benefit from these combinations, Garje emphasizes. The findings from these studies supported the FDA approvals of their respective regimens, Garje notes.

It is crucial to discern the specific patient subsets for which these PARP inhibitor combinations are indicated, as subtle differences exist between these regimens and indications, according to Garje. For instance, olaparib plus abiraterone and niraparib plus abiraterone are both approved by the FDA for patients with BRCA1/2-mutated mCRPC. In contrast, talazoparib plus enzalutamide is FDA approved for a broader population of patients with homologous recombination repair gene mutations. Evaluating the adverse effect profiles and potential drug-drug interactions of these regimens further aids in selecting the most suitable treatment options for individual patients, Garje says. The FDA approvals for these 3 PARP inhibitor–based combinations has improved the treatment paradigm in prostate cancer, and underscores the importance of employing genetic testing to identify patients who are eligible for each of these therapies, Garje concludes.